Impact of Femoral Medullary Canal Preservation During Primary Total Knee Arthroplasty on Early Perioperative Outcomes

Impact of Femoral Medullary Canal Preservation During Primary Total Knee Arthroplasty on Early Perioperative Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Femoral Medullary Canal Preservation During Primary Total Knee Arthroplasty on Early Perioperative Outcomes Chih-Wei Chang, Yen-Nien Chen, Lung-Hsuan Lin, Chyun-Yu Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8575044/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose- Intramedullary (IM) femoral referencing during total knee arthroplasty (TKA) has been associated with increased perioperative blood loss. This study aimed to evaluate whether a simplified extramedullary (EM) free-hand referencing technique, designed to preserve the femoral medullary canal, is associated with differences in perioperative bleeding-related parameters and alignment accuracy compared with conventional IM referencing. Methods- A retrospective cohort study was conducted including patients who underwent primary TKA using either IM or EM femoral referencing by a single surgeon. Perioperative hemoglobin change, calculated estimated blood loss, and postoperative D-dimer levels were analyzed as comparative bleeding-related parameters. Operative time, transfusion rates, early recovery indicators, and radiographic alignment outcomes were also assessed. All patients were managed under a standardized perioperative blood management protocol, including routine tranexamic acid administration. Results- A total of 125 TKAs were analyzed (IM: 60; EM: 65). Operative time was comparable between groups. The EM group demonstrated a smaller postoperative hemoglobin decrease (1.92 ± 0.8 vs. 2.35 ± 1.0 g/dL; p = 0.022) and lower calculated estimated blood loss (618.4 ± 291.5 vs. 755.8 ± 272.1 mL; p = 0.008). Postoperative D-dimer levels at 24 hours were lower in the EM group (p = 0.015) and were analyzed as an exploratory marker of perioperative physiological response. Transfusion rates were low and comparable between groups. Radiographic alignment accuracy did not differ significantly between techniques. Conclusion- Femoral medullary canal preservation using a simplified extramedullary free-hand referencing technique was associated with favorable perioperative bleeding-related parameters without compromising alignment accuracy or operative efficiency. This approach represents a practical alternative to intramedullary referencing in primary TKA and warrants further prospective evaluation. Level of Evidence III Total knee arthroplasty extramedullary femoral referencing medullary canal preservation perioperative outcomes alignment accuracy surgical technique Figures Figure 1 Figure 2 Figure 3 Introduction Knee osteoarthritis (OA) is a progressive degenerative joint disease that impairs mobility and quality of life. For advanced OA, total knee arthroplasty (TKA) remains the definitive surgical intervention, with more than 600,000 procedures performed annually in the United States and projected growth exceeding 1.2 million cases by 2030 [1]. Despite its clinical success, TKA is associated with perioperative challenges, including postoperative pain, thromboembolic events, and blood loss [2,3]. Intramedullary (IM) femoral referencing, the conventional alignment technique in TKA, requires violation of the femoral medullary canal. This maneuver has been associated with marrow embolization and activation of coagulation pathways, which may contribute to an increased perioperative bleeding-related burden. In contrast, extramedullary (EM) femoral referencing techniques avoid canal intrusion and have therefore been proposed as a less invasive alternative. However, evidence regarding their impact on perioperative blood loss remains inconsistent. Baldini et al. reported no significant difference in early postoperative drainage using EM femoral guides [4], whereas Kandel et al. and Jeon et al. observed reduced blood loss and smaller postoperative hemoglobin decreases with EM instrumentation [5,6]. Computer-assisted surgery (CAS), including navigation systems and patient-specific instrumentation (PSI), has further expanded the application of EM referencing. Although some studies have suggested improved alignment accuracy and reduced blood loss with CAS-assisted techniques [7–9], reported outcomes remain variable. Pietsch et al. demonstrated reduced postoperative drainage without significant differences in hemoglobin loss or transfusion rates [9], while Ajwani et al. and Thienpont et al. found no meaningful reduction in perioperative blood loss with CAS or PSI [11,12]. Our previous work similarly did not demonstrate a clear blood-sparing advantage of EM referencing, potentially influenced by prolonged operative duration or tourniquet time during early adoption [13]. Collectively, these findings underscore the importance of evaluating medullary canal preservation in routine primary TKA settings where operative time is comparable and the effect of canal violation can be more clearly isolated. Building on prior experience with EM instrumentation in complex cases involving retained hardware [14], we developed a simplified free-hand EM femoral referencing technique suitable for routine primary TKA. This approach eliminates the need for navigation markers, minimizes additional surgical exposure, and permits intraoperative assessment of limb alignment using standard anatomical landmarks and established alignment principles. With increasing surgical familiarity and workflow optimization, operative duration became comparable to that of conventional IM techniques, thereby enabling a more valid evaluation of the perioperative impact of femoral medullary canal preservation. In this context, the present retrospective cohort study compares perioperative outcomes between conventional IM femoral referencing and the simplified free-hand EM technique in primary TKA. The primary objective was to evaluate perioperative bleeding-related parameters. Secondary objectives included operative efficiency, early recovery indicators, and postoperative complications. Radiographic alignment accuracy was assessed to confirm technical comparability between techniques. We hypothesized that femoral medullary canal preservation using the EM technique would be associated with favorable perioperative bleeding-related parameters without compromising alignment accuracy or operative time. Although extramedullary referencing has been described in various forms, few studies have evaluated a simplified freehand technique performed without navigation or patient-specific instrumentation under operative conditions comparable to conventional intramedullary referencing. The study period also reflects a clinical workflow and perioperative blood management protocol that are no longer commonly encountered, providing a unique opportunity to examine the isolated physiological effect of medullary canal violation without confounding from modern technologies. These features allow the present investigation to address an aspect of TKA technique that is increasingly difficult to reproduce in contemporary practice. Materials and Methods Study Design and Patient Selection This retrospective cohort study was approved by the Institutional Review Board of the participating medical center (IRB No. A-ER-106-021). In accordance with institutional policy and ethical standards, the requirement for informed consent was waived due to the retrospective design and use of de-identified data. A consecutive series of adult patients who underwent unilateral primary total knee arthroplasty (TKA) between March 2013 and June 2014 were identified using Current Procedural Terminology (CPT) code 64164B. Patients were excluded if they had a diagnosis other than primary degenerative arthritis, a history of major knee surgery, revision or bilateral TKA, ongoing anticoagulation therapy, liver or renal failure, preoperative anemia (hemoglobin 35 or < 15 kg/m²) (Fig. 1 ). Patients were grouped according to the femoral alignment method used during the study period: IM group (March–October 2013) and EM group (November 2013–June 2014). Surgical Technique and Perioperative Blood Management All procedures were performed via a standard medial parapatellar approach by a single senior surgeon experienced in both intramedullary and extramedullary referencing techniques. Perioperative blood management (PBM) was applied uniformly and included tourniquet use (280–320 mmHg), omission of postoperative drains, meticulous electrocautery for subcutaneous hemostasis, a single intra-articular injection of tranexamic acid (10–15 mg/kg) mixed with 0.5% bupivacaine (100 mg/20 mL) at closure, and standardized transfusion thresholds. IM Group : Distal femoral and proximal tibial cuts were performed using conventional intramedullary guides, based on preoperative long-leg weight-bearing radiographs. The femorotibial angle (FTA), defined by the intersection of anatomic and mechanical axes, guided femoral jig placement. Following femoral cuts, the canal was sealed with an autologous bone plug [15]. Tibial alignment was established using a 9 mm stainless steel rod inserted into the intercondylar notch, with a 0° sagittal cutting jig. EM Group : The extramedullary alignment method used in this study was adapted from our previously published approach for conversion TKA in patients with retained hardware [14]. A horizontal line was marked on the proximal tibia using electrocautery, referencing the tibial shaft and anatomical landmarks with the knee flexed ≥ 90° (Fig. 2 a). Osteotomy was performed along this line, calibrated to preoperative measurements. The distal femoral cut was executed in extension, referencing a parallel line relative to the tibial cut (Fig. 2 b). Alignment was confirmed intraoperatively by distraction and bony contact between the two cuts (Figs. 2 c and 2 d). Remaining femoral cuts were completed using a commercial four-in-one jig, referencing Whiteside’s line. No canal sealing was required. All patients received cemented posterior-stabilized (PS) prostheses, including U2 Knee® (United Orthopedic Co., Taiwan) and Genesis II® (Smith & Nephew, New Zealand). Implant distribution was balanced between groups without systematic preference for either design. Postoperative Management All patients followed a standardized postoperative care pathway, including early mobilization, multimodal analgesia, and fluid supplementation. Thromboprophylaxis consisted of intravenous lysine acetylsalicylic acid (500 mg/day for 3 days), mechanical calf compression, and early ambulation. Discharge criteria included a stable wound, independent ambulation, and active knee flexion ≥ 90°. Outcome Measures Primary Outcome: Bleeding Profile The prespecified primary outcome was a composite perioperative bleeding profile, consisting of hemoglobin (Hb) drop and estimated blood loss (EBL). Hb and hematocrit (Hct) levels were recorded preoperatively and on postoperative days (POD) 1, 2, and 4. EBL was calculated using the Gross formula and Nadler’s equation [16,17], which are widely used in orthopedic research. Due to tourniquet use and absence of drains, hidden blood loss may be underestimated; therefore, maximum Hb drop was used as a surrogate marker. Secondary and Exploratory Outcomes Secondary and exploratory outcomes were assessed to further characterize perioperative safety, recovery, and thrombo-inflammatory response. Transfusion-related outcomes included the allogeneic blood transfusion rate, with transfusion triggered by a hemoglobin level < 8.0 g/dL or < 10.0 g/dL in symptomatic patients. To explore perioperative thrombo-inflammatory activation, D-dimer levels were measured preoperatively and at 24 hours postoperatively. Perioperative recovery parameters were evaluated using multiple clinical indicators. Breakthrough pain episodes were defined as visual analog scale (VAS) scores > 3 requiring rescue analgesia and were recorded by nursing staff during routine assessments every 4–6 hours and upon patient request. Total rescue narcotic consumption during hospitalization was documented. Functional recovery was assessed by time to achieve 90° of knee flexion and the ability to perform a straight leg raise. Length of hospital stay was recorded in days. Postoperative complications, including surgical site infection, deep vein thrombosis (DVT), and pulmonary embolism, were monitored during hospitalization and outpatient follow-up within 3 months. Statistical Analysis Data were analyzed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). No a priori sample size or power calculation was performed prior to data collection due to the retrospective design of the study. Continuous variables were tested for normality using the Shapiro–Wilk test. Normally distributed variables are reported as mean ± SD and compared using Student’s t‑test; non‑normal variables are reported as median (IQR) and compared using the Mann–Whitney U test. Categorical variables were presented as frequencies and percentages, and compared using chi-square or Fisher’s exact test, as appropriate. A two-tailed p-value < 0.05 was considered statistically significant. In addition to p-values, Cohen’s d was calculated for continuous variables to quantify effect sizes. Post hoc power analyses were performed for the primary bleeding-related outcomes using observed effect sizes and pooled standard deviations. Exploratory multivariable linear regression analyses were additionally performed to assess the independent association between femoral referencing technique and bleeding-related outcomes; these analyses are reported in the Supplementary Material. Results Patient Demographics and Baseline Characteristics A total of 125 primary TKA procedures were analyzed, including 60 in the IM group and 65 in the EM group. Baseline demographic characteristics are summarized in Table 1 . No statistically significant differences were observed between groups in age, sex distribution, body weight, height, admission hemoglobin level, or baseline D-dimer levels (all p > 0.05). Effect sizes for all comparisons were negligible to small, indicating that the groups were well matched at baseline. Table 1 Baseline characteristics Variable IM Group (n = 60) EM Group (n = 65) p-value Cohen’s d Age (years) 69.10 ± 7.90 70.30 ± 7.90 0.370 0.15 Gender (M/F) 16 / 44 17 / 48 0.910 (Chi-square) — Body weight (kg) 67.0 ± 10.90 68.50 ± 14.20 0.49 0.12 Body height (cm) 155.0 ± 7.90 155.30 ± 8.00 0.84 0.04 BMI (kg/m²) 27.90 ± 5.30 28.40 ± 6.62 0.576 0.01 Hemoglobin at admission (g/dL) 12.70 ± 1.41 12.60 ± 1.27 0.65 0.08 D-dimer at admission (ng/mL), median (IQR) 266.70 (231.20–302.20) 373.10 (204.15–542.05) 0.11 0.28 Values are mean ± SD unless otherwise indicated; D‑dimer at admission presented as median (IQR). p-values from t-test unless noted. Cohen’s d: 0.2 = small, 0.5 = moderate, 0.8 = large. Bleeding Profile and Hemodynamic Response Key bleeding-related outcomes are presented in Table 2 and illustrated in Fig. 3 . Mean operative (ischemic) time - measured from skin incision to closure - was comparable between groups (IM: 56.1 ± 11.8 min vs. EM: 56.5 ± 10.3 min; p = 0.84), indicating similar surgical efficiency despite differing alignment techniques. Table 2 Bleeding-related outcomes Variable IM Group (n = 60) EM Group (n = 65) Mean difference 95% CI (difference) p-value Cohen’s d Ischemic time (min) 56.1 ± 11.80 56.5 ± 10.30 -0.4 −4.80 to 4.00 0.840 0.04 Maximum Hb drop (g/dL) 2.35 ± 1.00 1.92 ± 0.80 0.43 0.11 to 0.75 0.022* 0.47 Estimated blood loss (mL) 755.80 ± 272.10 618.4 ± 291.5 137.40 38.6 to 236.20 0.008* 0.49 D-dimer at 24 hr postop (ng/mL), median (IQR) 1609.30 (1259.10–1959.50) 1186.60 (1049.50–1323.70) 422.70 99.0 to 746.40 0.015* 0.47 Transfusion rate (%) 3.3% (2/60) 3.0% (2/65) — — 0.940 (Fisher’s) — Total transfused units (all patients) 4 4 — — — — Values are mean ± SD unless stated otherwise; group difference = IM − EM. For D‑dimer at 24 hr postop this table shows median (IQR). 95% CIs for mean differences computed using SE = sqrt (SD12/n2) and CI = difference ± 1.96·SE. Tests: Student’s t‑test for continuous variables (two‑sided) and Fisher’s exact test for categorical counts; *p < 0.05. D‑dimer units: ng/mL (report assay/manufacturer and laboratory reference range in Methods). Transfusion events are sparse (IM 2/60, EM 2/65); interpret Fisher’s p with caution. Comparisons in this table are unadjusted. Exploratory multivariable analyses are presented separately in Supplementary Tables S1 and S2. The IM group demonstrated significantly greater Hb reduction (2.35 ± 1.0 vs. 1.92 ± 0.8 g/dL; p = 0.022, Cohen’s d = 0.47) and higher calculated blood loss (755.8 ± 272.1 vs. 618.4 ± 291.5 mL; p = 0.008, d = 0.49), both with moderate effect sizes. Postoperative D-dimer levels at 24 hours were higher in the IM group (1609.3 ± 1010.2 ng/mL) than in the EM group (1186.6 ± 816.3 ng/mL; p = 0.015, d = 0.47). Under identical transfusion thresholds, transfusion rates were low and comparable between groups (IM: 3.3% [2/60] vs. EM: 3.0% [2/65]; p = 0.94), and the total number of packed red blood cell units transfused was identical (4 units in each group). Exploratory multivariable analyses adjusting for demographic factors, baseline hemoglobin, D-dimer levels, and ischemic time yielded results consistent with the unadjusted comparisons and are presented in Supplementary Tables S1 and S2. Early Postoperative Recovery Early postoperative recovery outcomes are summarized in Table 3 . No statistically significant differences were observed between groups in length of hospital stay (IM: 6.74 ± 1.0 vs. EM: 6.71 ± 1.0 days; p = 0.84, d = 0.03), breakthrough pain episodes, or total rescue narcotic consumption. Table 3 Early Postoperative Outcomes Outcome Measure IM Group (n = 60) EM Group (n = 65) p-value Cohen’s d Inpatient stay (days) 6.74 ± 1.00 6.71 ± 1.00 0.840 0.03 Breakthrough pain (episodes), median (IQR) 3.50 (2.06–4.94) 3.20 (1.36–5.04) 0.380 0.14 Rescue narcotics (mg ME), median (IQR) 15.10 (9.32–20.88) 13.60 (6.77–20.43) 0.450 0.13 Time to active straight leg raise (days) 2.60 ± 0.90 2.30 ± 0.90 0.090 0.33 Time to 90° knee flexion (days) 3.10 ± 0.80 2.80 ± 0.90 0.060 0.35 Complications at clinical follow-ups None None — — Values are mean ± SD unless otherwise indicated. Breakthrough pain episodes and rescue narcotics are presented as median (IQR) because their distributions were non‑normal (Shapiro–Wilk). ME = morphine equivalent. Tests: Student’s t‑test for normally distributed variables; Mann–Whitney U test for non‑normal variables. Time to active straight leg raise showed a trend toward earlier recovery in the EM group (2.6 ± 0.9 vs. 2.3 ± 0.9 days; p = 0.09, d = 0.33). No postoperative complications—including surgical site infection, deep vein thrombosis, or pulmonary embolism—were observed in either group at the 2- and 6-week follow-ups. No additional adverse events were identified during the 3-month radiographic evaluation period. Radiographic Assessment Radiographic alignment outcomes are presented in Table 4 . Preoperative mechanical alignment did not differ significantly between groups (IM: 12.5 ± 6.1° vs. EM: 11.0 ± 5.2°; p = 0.18, d = 0.26). Postoperative mechanical alignment was nearly identical (IM: 2.76 ± 1.7° vs. EM: 2.74 ± 1.7°; p = 0.94, d = 0.01), indicating comparable coronal alignment accuracy. Table 4 Radiographic Measurements Radiographic Parameter IM Group (n = 60) EM Group (n = 65) p-value Cohen’s d Interpretation Preoperative mechanical alignment (°) 12.50 ± 6.10 11.00 ± 5.20 0.180 0.26 Small Postoperative mechanical alignment (°) 2.76 ± 1.70 2.74 ± 1.70 0.940 0.01 Negligible Femoral sagittal alignment (°) 3.83 ± 3.30 4.27 ± 3.90 0.500 0.12 Small Tibial sagittal alignment (°) 89.60 ± 4.60 89.90 ± 8.60 0.810 0.04 Negligible Alignment outliers* 18/60 (30.0%) 19/65 (29.2%) 0.92 (Chi-square) — No difference Values are mean ± SD unless otherwise indicated. *Outliers defined as deviation > 3° from planned mechanical alignment. Inter‑ and intra‑observer ICCs for radiographic measures were > 0.90 (see Methods). Femoral sagittal alignment was slightly more extended in the IM group (3.83 ± 3.3°) than in the EM group (4.27 ± 3.9°), although the difference was not statistically significant (p = 0.50, d = 0.12). Tibial sagittal alignment was also similar between groups (IM: 89.6 ± 4.6° vs. EM: 89.9 ± 8.6°; p = 0.81, d = 0.04). The proportion of alignment outliers—defined as deviation greater than 3° from the planned mechanical axis—was comparable between groups (IM: 30.0% vs. EM: 29.2%; p = 0.92), indicating equivalent radiographic precision between the extramedullary free-hand technique and conventional intramedullary referencing. Discussion This retrospective cohort study suggests that medullary preservation during primary total knee arthroplasty (TKA), achieved through a simplified extramedullary (EM) free-hand referencing technique, is associated with reduced perioperative bleeding. Compared with conventional intramedullary (IM) referencing, the EM group exhibited significantly lower hemoglobin drop, reduced calculated blood loss, and attenuated postoperative D-dimer elevation (Table 2 , Fig. 3 ), findings that are consistent with prior reports on medullary-sparing approaches [5–9]. Historically, EM referencing systems were evaluated primarily for alignment accuracy [3,18,19], while their potential hemostatic benefits remained underrecognized until the advent of computer-assisted surgery (CAS) [4–6]. However, studies examining CAS-assisted techniques have reported inconsistent effects on bleeding and recovery outcomes [4,5,11,13,20], likely influenced by prolonged operative duration—a known contributor to increased blood loss and systemic inflammatory response [10,21,22]. In the present study, ischemic time was nearly identical between groups (IM: 56.1 ± 11.8 min vs. EM: 56.5 ± 10.3 min; p = 0.84), supporting a fair comparison and reinforcing that the observed differences are attributable to medullary canal preservation rather than procedural confounding. The clinical environment during the study period offered a distinct opportunity to compare intramedullary and simplified freehand extramedullary referencing under nearly identical operative efficiency and perioperative protocols. As current TKA practice has shifted toward navigation, PSI, and enhanced recovery pathways, reproducing the same conditions for a contemporary comparison would no longer be feasible or ethically appropriate. This historical cohort therefore provides a rare setting in which the hemostatic impact of medullary canal violation can be evaluated with minimal procedural confounding, complementing and extending the findings of prior studies. The EM technique employed in this study relies on intraoperative visual cues and geometric parallelism between tibial and femoral cuts [14], achieving alignment accuracy comparable to IM referencing (Table 4 ) without reliance on navigation systems or patient-specific instrumentation. The proportion of alignment outliers was comparable between groups and consistent with previously reported ranges for conventional jig-based TKA, supporting the technical validity of the simplified EM approach. While reproducible in experienced hands, successful adoption requires accurate recognition of anatomical landmarks and consistent saw control. Structured supervision during early implementation may facilitate reliable execution and reduce technical variability. Although transfusion rates were low and statistically equivalent between groups (3.3% vs. 3.0%), the observed reduction in blood loss likely reflects the combined effect of medullary preservation and a standardized multimodal hemostatic strategy applied uniformly across cohorts [13,15,23–25]. Hb-based transfusion thresholds, while protocol-driven, may not fully capture early postoperative anemia, underscoring the importance of interpreting transfusion outcomes alongside quantitative blood loss measures and clinical context. Effect sizes were reported alongside p-values to emphasize the magnitude of observed differences. The moderate effect size for hemoglobin reduction (Cohen’s d = 0.47) suggests a clinically meaningful benefit of medullary preservation, even under contemporary blood management protocols. All patients received intra-articular tranexamic acid (TXA), which may have attenuated differences in transfusion requirements; however, uniform TXA use across both groups minimizes confounding and supports the validity of the comparison. Importantly, the EM group continued to demonstrate lower blood loss and hemoglobin decline despite TXA administration. Exploratory multivariable analyses, presented in the Supplementary Material, confirmed that extramedullary referencing remained independently associated with reduced hemoglobin drop and estimated blood loss after adjustment for relevant covariates. Bleeding following TKA is multifactorial [4,10], yet the consistent reduction in hemoglobin drop and postoperative D-dimer levels observed in the EM group underscores the additive value of avoiding intramedullary canal violation. Given the nonspecific nature of D-dimer and its sensitivity to surgical trauma and pharmacologic agents, the isolated elevation observed at 24 hours should not be interpreted as increased thrombotic risk. Rather, this exploratory finding may reflect a reduced systemic coagulation response associated with medullary preservation and warrants further prospective investigation. Although the primary objective focused on blood-sparing effects, early recovery parameters—including pain control, narcotic use, and time to straight leg raise—showed favorable trends in the EM group, albeit without statistical significance (Table 3 ). These findings align with prior comparisons between patient-specific instrumentation and conventional techniques [26,27] and may reflect reduced marrow trauma. Kalairajah et al. [28] previously demonstrated reduced cerebral embolic load during navigation-assisted TKA, supporting the concept that less invasive referencing strategies may confer systemic benefits. Considering the retrospective nature and modest sample size, the present study may have been underpowered to identify differences in early recovery. Furthermore, the use of clinical documentation rather than validated PROMs limits the assessment of patient-centered recovery, highlighting the importance of incorporating PROMs in future prospective investigations. Strengths and Limitations This study benefits from consecutive sampling, a uniform institutional blood management protocol, and consistent surgical technique. All procedures were performed by a single experienced surgeon, which minimized inter-surgeon variability and strengthened internal validity, although this may limit generalizability. Balanced ischemic time between groups further reduced procedural confounding, and objective hematologic endpoints were complemented by radiographic alignment assessment to support both physiological and technical inferences. Limitations include the retrospective, single-center design and the chronological allocation of IM and EM techniques, which may introduce selection and temporal biases. Although operative time was comparable between groups—reducing the likelihood of learning-curve effects—residual confounding cannot be excluded. The study was not powered for fully adjusted multivariable modeling, and the modest sample size may limit the detection of differences in secondary outcomes. Blood loss estimation relied on formula-based calculations without postoperative drains, which may underestimate hidden loss, although the same method was applied uniformly across groups. Pain and recovery assessments were derived from clinical documentation rather than validated PROMs, and follow-up was limited to the early postoperative period. Future studies incorporating prospective designs, standardized PROMs, and propensity-score methods are warranted to further address these limitations. Conclusions This retrospective comparative study suggests that preserving the femoral medullary canal during primary TKA is associated with reduced perioperative blood loss, as reflected by lower hemoglobin drop, calculated blood loss, and postoperative D-dimer levels. These hematologic advantages were achieved without compromising alignment accuracy or operative duration. Although canal preservation in this cohort was achieved using a simplified extramedullary approach, the findings highlight the potential physiological value of minimizing medullary violation itself. Prospective randomized studies are warranted to validate these observations and further define the role of medullary-sparing strategies in modern TKA. Declarations Ethics declarations Conflict of interest The authors declare that they have no competing interests. Ethical approval This study was approved by the Institutional Review Board of National Cheng Kung University Hospital (IRB No. A-ER-106-021). The requirement for informed consent was waived due to the retrospective design and use of de-identified data. Consent for publication Not applicable. No individual person’s data or identifiable images are included in this manuscript. 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Knee 7(3):151–155 Heyse TJ, Haas SB, Drinkwater D et al (2014) Intraarticular fibrinogen does not reduce blood loss in TKA: A randomized clinical trial. Clin Orthop Relat Res 472(1):272–276 Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialforEJOST.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8575044","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":585928076,"identity":"7fd77f7a-5eb5-42aa-bbbf-04b5df5cc824","order_by":0,"name":"Chih-Wei Chang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYDAC+ccHDiQY2DDzMzCwEasnLfHBg4o0dskGhBbGBvxacowNH5w5xG9wgFgtBgfOmEkkth2QNr6R/OzBhwoGeX6xA+yPefBpOdhWBtRyx9jsRpq54YwzDIYzZycwNuPVcph5G1DLs2SzGwlm0rxtDAkGt4FacvBpOcYActjh+s0z0r8RqeUMi7FBwpnDzAYSOUTaInmDLfFBQkUas8SZN2WSM85IAP2S2Dj7Dx4tfDeYDxz8AYrK9vRtEh8qbOT5pZMPfJyBRwsCCCSASAkGwjEJB/wHiFQ4CkbBKBgFIw4AAE9sUg/QV8F8AAAAAElFTkSuQmCC","orcid":"","institution":"National Chung Cheng University","correspondingAuthor":true,"prefix":"","firstName":"Chih-Wei","middleName":"","lastName":"Chang","suffix":""},{"id":585928077,"identity":"f1d90c73-30d2-48e6-95f4-853a30326bd4","order_by":1,"name":"Yen-Nien Chen","email":"","orcid":"","institution":"Asia University","correspondingAuthor":false,"prefix":"","firstName":"Yen-Nien","middleName":"","lastName":"Chen","suffix":""},{"id":585928078,"identity":"eb64edba-10c3-4ab8-bed8-ae81398c7c11","order_by":2,"name":"Lung-Hsuan Lin","email":"","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lung-Hsuan","middleName":"","lastName":"Lin","suffix":""},{"id":585928079,"identity":"e00e010d-5d54-49ac-bacc-8be453e114a4","order_by":3,"name":"Chyun-Yu Yang","email":"","orcid":"","institution":"Kuo General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chyun-Yu","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2026-01-11 17:23:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8575044/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8575044/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102297359,"identity":"5d75a4f1-dfd0-46c4-8762-a59bf3965bc1","added_by":"auto","created_at":"2026-02-10 10:27:11","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":128035,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient enrollment flowchart for the knee osteoarthritis study.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf 153 patients screened, those meeting inclusion criteria (ambulatory knee pain VAS \u0026gt; 3; K‑L grade ≥ II; procedure code 64164B) were considered; exclusions were alternate diagnosis (n = 5), prior major knee surgery (n = 3), revision/bilateral procedures (n = 4), incomplete therapy plan (n = 6), preoperative anemia (Hb \u0026lt; 10 g/dL; n = 4), low mental health score (n = 2), extreme BMI (BMI \u0026gt; 35 or \u0026lt; 15; n = 3), and refusal (n = 6). Final allocation by time period yielded Intramedullary (IM) group, n = 60 (Mar–Oct 2013), and Extramedullary (EM) group, n = 65 (Nov 2013–Jun 2014).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations: OA = osteoarthritis; VAS = visual analogue scale; K‑L = Kellgren–Lawrence; Hb = hemoglobin; BMI = body mass index.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1Patientenrollmentflowchartforthekneeosteoarthritisstudy.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8575044/v1/8ba1f630553e9a6e85cc1653.jpeg"},{"id":102210190,"identity":"0d1c5baa-d7e2-4d31-9f35-0eb01da0ffb0","added_by":"auto","created_at":"2026-02-09 12:18:43","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":184808,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExtramedullary (EM) referencing technique for primary total knee arthroplasty.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePanels a–d illustrate the tibia-cut-based EM technique used for intraoperative bone referencing and alignment verification. Panel e shows comparable postoperative coronal alignment in both intramedullary (IM) and EM groups.\u003c/p\u003e\n\u003cp\u003ea. A horizontal cut line is marked on the proximal tibia using electrocautery, referencing the tibial shaft (blue dotted line).\u003c/p\u003e\n\u003cp\u003eb. The proximal tibial cut (PTC; blue line) is used to guide a parallel cut line on the distal femur (DFC).\u003c/p\u003e\n\u003cp\u003ec. Parallelism and extension gap between PTC and DFC are verified intraoperatively by applying even distraction to the lower limb.\u003c/p\u003e\n\u003cp\u003ed. Coronal alignment and osteotomy adequacy are confirmed by full contact (white arrows) between PTC and DFC.\u003c/p\u003e\n\u003cp\u003ee. Postoperative radiographs demonstrate comparable alignment outcomes in both groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations: EM = extramedullary; IM = intramedullary; TKA = total knee arthroplasty; PTC = proximal tibial cut; DFC = distal femur cut.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.EMreferencingtechniqueforprimarytotalkneearthroplasty.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8575044/v1/d0b02b19e2092cbefd91ce47.jpeg"},{"id":102210188,"identity":"1860a5d5-4f5f-49f9-b3ac-39cca2986cde","added_by":"auto","created_at":"2026-02-09 12:18:43","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":54909,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePostoperative D-dimer levels at 24 hours in the IM and EM groups.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBox plots display absolute D-dimer concentrations (ng/mL) measured at admission and 24 hours after surgery, showing median, interquartile range, and outliers. With comparable baseline levels, the IM group exhibited significantly higher D-dimer values than the EM group at 24 hours (1609.3 ± 1010.2 vs. 1186.6 ± 816.3 ng/mL, p = 0.015), suggesting a greater systemic coagulation response. The p-value is visually emphasized using Artstar to highlight statistical significance.\u003c/p\u003e","description":"","filename":"Figure3.PostoperativeDdimerlevelsat24hoursintheIMandEMgroups.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8575044/v1/eb1cdfa1518c81dac1e7e41b.jpeg"},{"id":105728964,"identity":"07d1e544-26b8-4c54-9350-b015e382822f","added_by":"auto","created_at":"2026-03-30 11:13:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1380462,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8575044/v1/ac1a2023-ee1f-478b-a788-e66aa1aeaba2.pdf"},{"id":102210186,"identity":"8b9dc2e6-3d9d-40bd-acf4-9b4c07cc2eec","added_by":"auto","created_at":"2026-02-09 12:18:43","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15493,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialforEJOST.docx","url":"https://assets-eu.researchsquare.com/files/rs-8575044/v1/b95818a62413aa31aca1055a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Femoral Medullary Canal Preservation During Primary Total Knee Arthroplasty on Early Perioperative Outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKnee osteoarthritis (OA) is a progressive degenerative joint disease that impairs mobility and quality of life. For advanced OA, total knee arthroplasty (TKA) remains the definitive surgical intervention, with more than 600,000 procedures performed annually in the United States and projected growth exceeding 1.2\u0026nbsp;million cases by 2030 [1]. Despite its clinical success, TKA is associated with perioperative challenges, including postoperative pain, thromboembolic events, and blood loss [2,3].\u003c/p\u003e \u003cp\u003eIntramedullary (IM) femoral referencing, the conventional alignment technique in TKA, requires violation of the femoral medullary canal. This maneuver has been associated with marrow embolization and activation of coagulation pathways, which may contribute to an increased perioperative bleeding-related burden. In contrast, extramedullary (EM) femoral referencing techniques avoid canal intrusion and have therefore been proposed as a less invasive alternative. However, evidence regarding their impact on perioperative blood loss remains inconsistent. Baldini et al. reported no significant difference in early postoperative drainage using EM femoral guides [4], whereas Kandel et al. and Jeon et al. observed reduced blood loss and smaller postoperative hemoglobin decreases with EM instrumentation [5,6].\u003c/p\u003e \u003cp\u003eComputer-assisted surgery (CAS), including navigation systems and patient-specific instrumentation (PSI), has further expanded the application of EM referencing. Although some studies have suggested improved alignment accuracy and reduced blood loss with CAS-assisted techniques [7\u0026ndash;9], reported outcomes remain variable. Pietsch et al. demonstrated reduced postoperative drainage without significant differences in hemoglobin loss or transfusion rates [9], while Ajwani et al. and Thienpont et al. found no meaningful reduction in perioperative blood loss with CAS or PSI [11,12]. Our previous work similarly did not demonstrate a clear blood-sparing advantage of EM referencing, potentially influenced by prolonged operative duration or tourniquet time during early adoption [13]. Collectively, these findings underscore the importance of evaluating medullary canal preservation in routine primary TKA settings where operative time is comparable and the effect of canal violation can be more clearly isolated.\u003c/p\u003e \u003cp\u003eBuilding on prior experience with EM instrumentation in complex cases involving retained hardware [14], we developed a simplified free-hand EM femoral referencing technique suitable for routine primary TKA. This approach eliminates the need for navigation markers, minimizes additional surgical exposure, and permits intraoperative assessment of limb alignment using standard anatomical landmarks and established alignment principles. With increasing surgical familiarity and workflow optimization, operative duration became comparable to that of conventional IM techniques, thereby enabling a more valid evaluation of the perioperative impact of femoral medullary canal preservation.\u003c/p\u003e \u003cp\u003eIn this context, the present retrospective cohort study compares perioperative outcomes between conventional IM femoral referencing and the simplified free-hand EM technique in primary TKA. The primary objective was to evaluate perioperative bleeding-related parameters. Secondary objectives included operative efficiency, early recovery indicators, and postoperative complications. Radiographic alignment accuracy was assessed to confirm technical comparability between techniques. We hypothesized that femoral medullary canal preservation using the EM technique would be associated with favorable perioperative bleeding-related parameters without compromising alignment accuracy or operative time.\u003c/p\u003e \u003cp\u003eAlthough extramedullary referencing has been described in various forms, few studies have evaluated a simplified freehand technique performed without navigation or patient-specific instrumentation under operative conditions comparable to conventional intramedullary referencing. The study period also reflects a clinical workflow and perioperative blood management protocol that are no longer commonly encountered, providing a unique opportunity to examine the isolated physiological effect of medullary canal violation without confounding from modern technologies. These features allow the present investigation to address an aspect of TKA technique that is increasingly difficult to reproduce in contemporary practice.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Patient Selection\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study was approved by the Institutional Review Board of the participating medical center (IRB No. A-ER-106-021). In accordance with institutional policy and ethical standards, the requirement for informed consent was waived due to the retrospective design and use of de-identified data.\u003c/p\u003e \u003cp\u003eA consecutive series of adult patients who underwent unilateral primary total knee arthroplasty (TKA) between March 2013 and June 2014 were identified using Current Procedural Terminology (CPT) code 64164B. Patients were excluded if they had a diagnosis other than primary degenerative arthritis, a history of major knee surgery, revision or bilateral TKA, ongoing anticoagulation therapy, liver or renal failure, preoperative anemia (hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;10.0 g/dL), or morbid obesity or underweight status (BMI\u0026thinsp;\u0026gt;\u0026thinsp;35 or \u0026lt;\u0026thinsp;15 kg/m\u0026sup2;) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients were grouped according to the femoral alignment method used during the study period: IM group (March\u0026ndash;October 2013) and EM group (November 2013\u0026ndash;June 2014).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurgical Technique and Perioperative Blood Management\u003c/h3\u003e\n\u003cp\u003eAll procedures were performed via a standard medial parapatellar approach by a single senior surgeon experienced in both intramedullary and extramedullary referencing techniques. Perioperative blood management (PBM) was applied uniformly and included tourniquet use (280\u0026ndash;320 mmHg), omission of postoperative drains, meticulous electrocautery for subcutaneous hemostasis, a single intra-articular injection of tranexamic acid (10\u0026ndash;15 mg/kg) mixed with 0.5% bupivacaine (100 mg/20 mL) at closure, and standardized transfusion thresholds.\u003c/p\u003e \u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eIM Group\u003c/b\u003e: Distal femoral and proximal tibial cuts were performed using conventional intramedullary guides, based on preoperative long-leg weight-bearing radiographs. The femorotibial angle (FTA), defined by the intersection of anatomic and mechanical axes, guided femoral jig placement. Following femoral cuts, the canal was sealed with an autologous bone plug [15]. Tibial alignment was established using a 9 mm stainless steel rod inserted into the intercondylar notch, with a 0\u0026deg; sagittal cutting jig.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eEM Group\u003c/b\u003e: The extramedullary alignment method used in this study was adapted from our previously published approach for conversion TKA in patients with retained hardware [14]. A horizontal line was marked on the proximal tibia using electrocautery, referencing the tibial shaft and anatomical landmarks with the knee flexed\u0026thinsp;\u0026ge;\u0026thinsp;90\u0026deg; (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Osteotomy was performed along this line, calibrated to preoperative measurements. The distal femoral cut was executed in extension, referencing a parallel line relative to the tibial cut (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Alignment was confirmed intraoperatively by distraction and bony contact between the two cuts (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). Remaining femoral cuts were completed using a commercial four-in-one jig, referencing Whiteside\u0026rsquo;s line. No canal sealing was required.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAll patients received cemented posterior-stabilized (PS) prostheses, including U2 Knee\u0026reg; (United Orthopedic Co., Taiwan) and Genesis II\u0026reg; (Smith \u0026amp; Nephew, New Zealand). Implant distribution was balanced between groups without systematic preference for either design.\u003c/p\u003e\n\u003ch3\u003ePostoperative Management\u003c/h3\u003e\n\u003cp\u003eAll patients followed a standardized postoperative care pathway, including early mobilization, multimodal analgesia, and fluid supplementation. Thromboprophylaxis consisted of intravenous lysine acetylsalicylic acid (500 mg/day for 3 days), mechanical calf compression, and early ambulation. Discharge criteria included a stable wound, independent ambulation, and active knee flexion\u0026thinsp;\u0026ge;\u0026thinsp;90\u0026deg;.\u003c/p\u003e\n\u003ch3\u003eOutcome Measures\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePrimary Outcome: Bleeding Profile\u003c/h2\u003e \u003cp\u003eThe prespecified primary outcome was a composite perioperative bleeding profile, consisting of hemoglobin (Hb) drop and estimated blood loss (EBL). Hb and hematocrit (Hct) levels were recorded preoperatively and on postoperative days (POD) 1, 2, and 4. EBL was calculated using the Gross formula and Nadler\u0026rsquo;s equation [16,17], which are widely used in orthopedic research. Due to tourniquet use and absence of drains, hidden blood loss may be underestimated; therefore, maximum Hb drop was used as a surrogate marker.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSecondary and Exploratory Outcomes\u003c/h2\u003e \u003cp\u003eSecondary and exploratory outcomes were assessed to further characterize perioperative safety, recovery, and thrombo-inflammatory response.\u003c/p\u003e \u003cp\u003eTransfusion-related outcomes included the allogeneic blood transfusion rate, with transfusion triggered by a hemoglobin level\u0026thinsp;\u0026lt;\u0026thinsp;8.0 g/dL or \u0026lt;\u0026thinsp;10.0 g/dL in symptomatic patients. To explore perioperative thrombo-inflammatory activation, D-dimer levels were measured preoperatively and at 24 hours postoperatively.\u003c/p\u003e \u003cp\u003ePerioperative recovery parameters were evaluated using multiple clinical indicators. Breakthrough pain episodes were defined as visual analog scale (VAS) scores\u0026thinsp;\u0026gt;\u0026thinsp;3 requiring rescue analgesia and were recorded by nursing staff during routine assessments every 4\u0026ndash;6 hours and upon patient request. Total rescue narcotic consumption during hospitalization was documented. Functional recovery was assessed by time to achieve 90\u0026deg; of knee flexion and the ability to perform a straight leg raise. Length of hospital stay was recorded in days.\u003c/p\u003e \u003cp\u003ePostoperative complications, including surgical site infection, deep vein thrombosis (DVT), and pulmonary embolism, were monitored during hospitalization and outpatient follow-up within 3 months.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). No a priori sample size or power calculation was performed prior to data collection due to the retrospective design of the study.\u003c/p\u003e \u003cp\u003eContinuous variables were tested for normality using the Shapiro\u0026ndash;Wilk test. Normally distributed variables are reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and compared using Student\u0026rsquo;s t‑test; non‑normal variables are reported as median (IQR) and compared using the Mann\u0026ndash;Whitney U test. Categorical variables were presented as frequencies and percentages, and compared using chi-square or Fisher\u0026rsquo;s exact test, as appropriate. A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. In addition to p-values, Cohen\u0026rsquo;s d was calculated for continuous variables to quantify effect sizes. Post hoc power analyses were performed for the primary bleeding-related outcomes using observed effect sizes and pooled standard deviations. Exploratory multivariable linear regression analyses were additionally performed to assess the independent association between femoral referencing technique and bleeding-related outcomes; these analyses are reported in the Supplementary Material.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient Demographics and Baseline Characteristics\u003c/h2\u003e \u003cp\u003eA total of 125 primary TKA procedures were analyzed, including 60 in the IM group and 65 in the EM group. Baseline demographic characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No statistically significant differences were observed between groups in age, sex distribution, body weight, height, admission hemoglobin level, or baseline D-dimer levels (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Effect sizes for all comparisons were negligible to small, indicating that the groups were well matched at baseline.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIM Group (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEM Group (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCohen\u0026rsquo;s d\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.10\u0026thinsp;\u0026plusmn;\u0026thinsp;7.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.30\u0026thinsp;\u0026plusmn;\u0026thinsp;7.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 / 44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 / 48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.910 (Chi-square)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody weight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.50\u0026thinsp;\u0026plusmn;\u0026thinsp;14.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody height (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155.30\u0026thinsp;\u0026plusmn;\u0026thinsp;8.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.90\u0026thinsp;\u0026plusmn;\u0026thinsp;5.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.40\u0026thinsp;\u0026plusmn;\u0026thinsp;6.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.576\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin at admission (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer at admission (ng/mL), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266.70 (231.20\u0026ndash;302.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e373.10 (204.15\u0026ndash;542.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD unless otherwise indicated; D‑dimer at admission presented as median (IQR). p-values from t-test unless noted. Cohen\u0026rsquo;s d: 0.2\u0026thinsp;=\u0026thinsp;small, 0.5\u0026thinsp;=\u0026thinsp;moderate, 0.8\u0026thinsp;=\u0026thinsp;large.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eBleeding Profile and Hemodynamic Response\u003c/h2\u003e \u003cp\u003eKey bleeding-related outcomes are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Mean operative (ischemic) time - measured from skin incision to closure - was comparable between groups (IM: 56.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 min vs. EM: 56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3 min; p\u0026thinsp;=\u0026thinsp;0.84), indicating similar surgical efficiency despite differing alignment techniques.\u003c/p\u003e \u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBleeding-related outcomes\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIM Group (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEM Group (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMean difference\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95% CI (difference)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCohen\u0026rsquo;s d\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic time (min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026minus;4.80 to 4.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.840\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum Hb drop (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.11 to 0.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.022*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.47\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEstimated blood loss (mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e755.80\u0026thinsp;\u0026plusmn;\u0026thinsp;272.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e618.4\u0026thinsp;\u0026plusmn;\u0026thinsp;291.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e137.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38.6 to 236.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.008*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eD-dimer at 24 hr postop (ng/mL), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1609.30 (1259.10\u0026ndash;1959.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1186.60 (1049.50\u0026ndash;1323.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e422.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e99.0 to 746.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.015*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.47\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTransfusion rate (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3% (2/60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0% (2/65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.940 (Fisher\u0026rsquo;s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal transfused units (all patients)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD unless stated otherwise; group difference\u0026thinsp;=\u0026thinsp;IM\u0026thinsp;\u0026minus;\u0026thinsp;EM. For D‑dimer at 24 hr postop this table shows median (IQR). 95% CIs for mean differences computed using SE\u0026thinsp;=\u0026thinsp;sqrt (SD12/n2) and CI\u0026thinsp;=\u0026thinsp;difference\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u0026middot;SE. Tests: Student\u0026rsquo;s t‑test for continuous variables (two‑sided) and Fisher\u0026rsquo;s exact test for categorical counts; *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. D‑dimer units: ng/mL (report assay/manufacturer and laboratory reference range in Methods). Transfusion events are sparse (IM 2/60, EM 2/65); interpret Fisher\u0026rsquo;s p with caution. Comparisons in this table are unadjusted. Exploratory multivariable analyses are presented separately in Supplementary Tables S1 and S2.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe IM group demonstrated significantly greater Hb reduction (2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 vs. 1.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 g/dL; p\u0026thinsp;=\u0026thinsp;0.022, Cohen\u0026rsquo;s d\u0026thinsp;=\u0026thinsp;0.47) and higher calculated blood loss (755.8\u0026thinsp;\u0026plusmn;\u0026thinsp;272.1 vs. 618.4\u0026thinsp;\u0026plusmn;\u0026thinsp;291.5 mL; p\u0026thinsp;=\u0026thinsp;0.008, d\u0026thinsp;=\u0026thinsp;0.49), both with moderate effect sizes.\u003c/p\u003e \u003cp\u003ePostoperative D-dimer levels at 24 hours were higher in the IM group (1609.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1010.2 ng/mL) than in the EM group (1186.6\u0026thinsp;\u0026plusmn;\u0026thinsp;816.3 ng/mL; p\u0026thinsp;=\u0026thinsp;0.015, d\u0026thinsp;=\u0026thinsp;0.47). Under identical transfusion thresholds, transfusion rates were low and comparable between groups (IM: 3.3% [2/60] vs. EM: 3.0% [2/65]; p\u0026thinsp;=\u0026thinsp;0.94), and the total number of packed red blood cell units transfused was identical (4 units in each group).\u003c/p\u003e \u003cp\u003eExploratory multivariable analyses adjusting for demographic factors, baseline hemoglobin, D-dimer levels, and ischemic time yielded results consistent with the unadjusted comparisons and are presented in Supplementary Tables S1 and S2.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEarly Postoperative Recovery\u003c/h2\u003e \u003cp\u003eEarly postoperative recovery outcomes are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. No statistically significant differences were observed between groups in length of hospital stay (IM: 6.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 vs. EM: 6.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 days; p\u0026thinsp;=\u0026thinsp;0.84, d\u0026thinsp;=\u0026thinsp;0.03), breakthrough pain episodes, or total rescue narcotic consumption.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEarly Postoperative Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome Measure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIM Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEM Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCohen\u0026rsquo;s d\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreakthrough pain (episodes), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.50 (2.06\u0026ndash;4.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.20 (1.36\u0026ndash;5.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRescue narcotics (mg ME), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.10 (9.32\u0026ndash;20.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.60 (6.77\u0026ndash;20.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to active straight leg raise (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to 90\u0026deg; knee flexion (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications at clinical follow-ups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD unless otherwise indicated. Breakthrough pain episodes and rescue narcotics are presented as median (IQR) because their distributions were non‑normal (Shapiro\u0026ndash;Wilk). ME\u0026thinsp;=\u0026thinsp;morphine equivalent. Tests: Student\u0026rsquo;s t‑test for normally distributed variables; Mann\u0026ndash;Whitney U test for non‑normal variables.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTime to active straight leg raise showed a trend toward earlier recovery in the EM group (2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 vs. 2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 days; p\u0026thinsp;=\u0026thinsp;0.09, d\u0026thinsp;=\u0026thinsp;0.33).\u003c/p\u003e \u003cp\u003eNo postoperative complications\u0026mdash;including surgical site infection, deep vein thrombosis, or pulmonary embolism\u0026mdash;were observed in either group at the 2- and 6-week follow-ups. No additional adverse events were identified during the 3-month radiographic evaluation period.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eRadiographic Assessment\u003c/h2\u003e \u003cp\u003eRadiographic alignment outcomes are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Preoperative mechanical alignment did not differ significantly between groups (IM: 12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u0026deg; vs. EM: 11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u0026deg;; p\u0026thinsp;=\u0026thinsp;0.18, d\u0026thinsp;=\u0026thinsp;0.26). Postoperative mechanical alignment was nearly identical (IM: 2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u0026deg; vs. EM: 2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u0026deg;; p\u0026thinsp;=\u0026thinsp;0.94, d\u0026thinsp;=\u0026thinsp;0.01), indicating comparable coronal alignment accuracy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRadiographic Measurements\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiographic Parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIM Group (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEM Group (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCohen\u0026rsquo;s d\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInterpretation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative mechanical alignment (\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.50\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.00\u0026thinsp;\u0026plusmn;\u0026thinsp;5.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSmall\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative mechanical alignment (\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.940\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNegligible\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoral sagittal alignment (\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.27\u0026thinsp;\u0026plusmn;\u0026thinsp;3.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSmall\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTibial sagittal alignment (\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89.60\u0026thinsp;\u0026plusmn;\u0026thinsp;4.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.90\u0026thinsp;\u0026plusmn;\u0026thinsp;8.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.810\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNegligible\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlignment outliers*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/60 (30.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19/65 (29.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92 (Chi-square)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo difference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD unless otherwise indicated. *Outliers defined as deviation\u0026thinsp;\u0026gt;\u0026thinsp;3\u0026deg; from planned mechanical alignment. Inter‑ and intra‑observer ICCs for radiographic measures were \u0026gt;\u0026thinsp;0.90 (see Methods).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFemoral sagittal alignment was slightly more extended in the IM group (3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u0026deg;) than in the EM group (4.27\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u0026deg;), although the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.50, d\u0026thinsp;=\u0026thinsp;0.12). Tibial sagittal alignment was also similar between groups (IM: 89.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u0026deg; vs. EM: 89.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u0026deg;; p\u0026thinsp;=\u0026thinsp;0.81, d\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e \u003cp\u003eThe proportion of alignment outliers\u0026mdash;defined as deviation greater than 3\u0026deg; from the planned mechanical axis\u0026mdash;was comparable between groups (IM: 30.0% vs. EM: 29.2%; p\u0026thinsp;=\u0026thinsp;0.92), indicating equivalent radiographic precision between the extramedullary free-hand technique and conventional intramedullary referencing.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective cohort study suggests that medullary preservation during primary total knee arthroplasty (TKA), achieved through a simplified extramedullary (EM) free-hand referencing technique, is associated with reduced perioperative bleeding. Compared with conventional intramedullary (IM) referencing, the EM group exhibited significantly lower hemoglobin drop, reduced calculated blood loss, and attenuated postoperative D-dimer elevation (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), findings that are consistent with prior reports on medullary-sparing approaches [5\u0026ndash;9].\u003c/p\u003e \u003cp\u003eHistorically, EM referencing systems were evaluated primarily for alignment accuracy [3,18,19], while their potential hemostatic benefits remained underrecognized until the advent of computer-assisted surgery (CAS) [4\u0026ndash;6]. However, studies examining CAS-assisted techniques have reported inconsistent effects on bleeding and recovery outcomes [4,5,11,13,20], likely influenced by prolonged operative duration\u0026mdash;a known contributor to increased blood loss and systemic inflammatory response [10,21,22]. In the present study, ischemic time was nearly identical between groups (IM: 56.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 min vs. EM: 56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3 min; p\u0026thinsp;=\u0026thinsp;0.84), supporting a fair comparison and reinforcing that the observed differences are attributable to medullary canal preservation rather than procedural confounding. The clinical environment during the study period offered a distinct opportunity to compare intramedullary and simplified freehand extramedullary referencing under nearly identical operative efficiency and perioperative protocols. As current TKA practice has shifted toward navigation, PSI, and enhanced recovery pathways, reproducing the same conditions for a contemporary comparison would no longer be feasible or ethically appropriate. This historical cohort therefore provides a rare setting in which the hemostatic impact of medullary canal violation can be evaluated with minimal procedural confounding, complementing and extending the findings of prior studies.\u003c/p\u003e \u003cp\u003eThe EM technique employed in this study relies on intraoperative visual cues and geometric parallelism between tibial and femoral cuts [14], achieving alignment accuracy comparable to IM referencing (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) without reliance on navigation systems or patient-specific instrumentation. The proportion of alignment outliers was comparable between groups and consistent with previously reported ranges for conventional jig-based TKA, supporting the technical validity of the simplified EM approach. While reproducible in experienced hands, successful adoption requires accurate recognition of anatomical landmarks and consistent saw control. Structured supervision during early implementation may facilitate reliable execution and reduce technical variability.\u003c/p\u003e \u003cp\u003eAlthough transfusion rates were low and statistically equivalent between groups (3.3% vs. 3.0%), the observed reduction in blood loss likely reflects the combined effect of medullary preservation and a standardized multimodal hemostatic strategy applied uniformly across cohorts [13,15,23\u0026ndash;25]. Hb-based transfusion thresholds, while protocol-driven, may not fully capture early postoperative anemia, underscoring the importance of interpreting transfusion outcomes alongside quantitative blood loss measures and clinical context.\u003c/p\u003e \u003cp\u003eEffect sizes were reported alongside p-values to emphasize the magnitude of observed differences. The moderate effect size for hemoglobin reduction (Cohen\u0026rsquo;s d\u0026thinsp;=\u0026thinsp;0.47) suggests a clinically meaningful benefit of medullary preservation, even under contemporary blood management protocols. All patients received intra-articular tranexamic acid (TXA), which may have attenuated differences in transfusion requirements; however, uniform TXA use across both groups minimizes confounding and supports the validity of the comparison. Importantly, the EM group continued to demonstrate lower blood loss and hemoglobin decline despite TXA administration. Exploratory multivariable analyses, presented in the Supplementary Material, confirmed that extramedullary referencing remained independently associated with reduced hemoglobin drop and estimated blood loss after adjustment for relevant covariates.\u003c/p\u003e \u003cp\u003eBleeding following TKA is multifactorial [4,10], yet the consistent reduction in hemoglobin drop and postoperative D-dimer levels observed in the EM group underscores the additive value of avoiding intramedullary canal violation. Given the nonspecific nature of D-dimer and its sensitivity to surgical trauma and pharmacologic agents, the isolated elevation observed at 24 hours should not be interpreted as increased thrombotic risk. Rather, this exploratory finding may reflect a reduced systemic coagulation response associated with medullary preservation and warrants further prospective investigation.\u003c/p\u003e \u003cp\u003eAlthough the primary objective focused on blood-sparing effects, early recovery parameters\u0026mdash;including pain control, narcotic use, and time to straight leg raise\u0026mdash;showed favorable trends in the EM group, albeit without statistical significance (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). These findings align with prior comparisons between patient-specific instrumentation and conventional techniques [26,27] and may reflect reduced marrow trauma. Kalairajah et al. [28] previously demonstrated reduced cerebral embolic load during navigation-assisted TKA, supporting the concept that less invasive referencing strategies may confer systemic benefits. Considering the retrospective nature and modest sample size, the present study may have been underpowered to identify differences in early recovery. Furthermore, the use of clinical documentation rather than validated PROMs limits the assessment of patient-centered recovery, highlighting the importance of incorporating PROMs in future prospective investigations.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eThis study benefits from consecutive sampling, a uniform institutional blood management protocol, and consistent surgical technique. All procedures were performed by a single experienced surgeon, which minimized inter-surgeon variability and strengthened internal validity, although this may limit generalizability. Balanced ischemic time between groups further reduced procedural confounding, and objective hematologic endpoints were complemented by radiographic alignment assessment to support both physiological and technical inferences.\u003c/p\u003e \u003cp\u003eLimitations include the retrospective, single-center design and the chronological allocation of IM and EM techniques, which may introduce selection and temporal biases. Although operative time was comparable between groups\u0026mdash;reducing the likelihood of learning-curve effects\u0026mdash;residual confounding cannot be excluded. The study was not powered for fully adjusted multivariable modeling, and the modest sample size may limit the detection of differences in secondary outcomes. Blood loss estimation relied on formula-based calculations without postoperative drains, which may underestimate hidden loss, although the same method was applied uniformly across groups. Pain and recovery assessments were derived from clinical documentation rather than validated PROMs, and follow-up was limited to the early postoperative period. Future studies incorporating prospective designs, standardized PROMs, and propensity-score methods are warranted to further address these limitations.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis retrospective comparative study suggests that preserving the femoral medullary canal during primary TKA is associated with reduced perioperative blood loss, as reflected by lower hemoglobin drop, calculated blood loss, and postoperative D-dimer levels. These hematologic advantages were achieved without compromising alignment accuracy or operative duration. Although canal preservation in this cohort was achieved using a simplified extramedullary approach, the findings highlight the potential physiological value of minimizing medullary violation itself. Prospective randomized studies are warranted to validate these observations and further define the role of medullary-sparing strategies in modern TKA.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e \u003cb\u003eEthics declarations\u003c/b\u003e \u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eConflict of interest\u003c/strong\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003e This study was approved by the Institutional Review Board of National Cheng Kung University Hospital (IRB No. A-ER-106-021). The requirement for informed consent was waived due to the retrospective design and use of de-identified data.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable. No individual person\u0026rsquo;s data or identifiable images are included in this manuscript.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInformed consent\u003c/strong\u003e \u003cp\u003e Because this study used de-identified retrospective data, informed consent for participation was waived by the Institutional Review Board.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received no external funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eC.-W. Chang: conceptualization, investigation, original draft preparation;Y.-N. Chen: methodology, formal analysis, review and editing;C.-Y. Yang: data curation, supervision;L.-H. Lin: data curation, visualization.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMoldovan F, Gligor A, Moldovan L, Bataga T (2023) An Investigation for Future Practice of Elective Hip and Knee Arthroplasties during COVID-19 in Romania. Medicina 59(2):314\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFahmy NR, Chandler HP, Danylchuk K, Matta EB, Sunder N, Siliski JM (1990) Blood-gas and circulatory changes during total knee replacement: Role of the intramedullary alignment rod. J Bone Joint Surg Am 72(1):19\u0026ndash;26\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIshii Y, Ohmori G, Bechtold JE, Gustilo RB (1995) Extramedullary versus intramedullary alignment guides in total knee arthroplasty. Clin Orthop Relat Res ;(318):167\u0026ndash;175\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaldini A, Adravanti P (2008) Less invasive TKA: extramedullary femoral reference without navigation. Clin Orthop Relat Res 466(11):2694\u0026ndash;2700\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKandel L, Vasili C, Kirsh G (2006) Extramedullary femoral alignment instrumentation reduces blood loss after uncemented total knee arthroplasty. J Knee Surg 19(4):256\u0026ndash;258\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeon SH, Kim JH, Lee JM, Seo ES (2012) Efficacy of extramedullary femoral component alignment guide system for blood saving after total knee arthroplasty. Knee Surg Relat Res 24(2):99\u0026ndash;103\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChauhan SK, Scott RG, Breidahl W, Beaver RJ (2004) Computer-assisted knee arthroplasty versus a conventional jig-based technique: A randomised, prospective trial. J Bone Joint Surg Br 86(3):372\u0026ndash;377\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalairajah Y, Simpson D, Cossey AJ, Verrall GM, Spriggins AJ (2005) Blood loss after total knee replacement: Effects of computer-assisted surgery. J Bone Joint Surg Br 87(11):1480\u0026ndash;1482\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePietsch M, Djahani O, Zweiger C et al (2013) Custom-fit minimally invasive total knee arthroplasty: Effect on blood loss and early clinical outcomes. Knee Surg Sports Traumatol Arthrosc 21(10):2234\u0026ndash;2240\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeon VJ, Lengua MA, Calvo V, Lison AJ (2017) Use of patient-specific cutting blocks reduces blood loss after total knee arthroplasty. Eur J Orthop Surg Traumatol 27(2):273\u0026ndash;277\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAjwani SH, Jones M, Jarratt JW, Shepard GJ, Ryan WG (2012) Computer assisted versus conventional total knee replacement: A comparison of tourniquet time, blood loss and length of stay. Knee 19(5):606\u0026ndash;610\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThienpont E, Grosu I, Paternostre F, Schwab PE, Yombi JC (2015) The use of patient specific instruments does not reduce blood loss during minimally invasive total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 23(7):2055\u0026ndash;2060\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang CW, Wu PT, Yang CY (2010) Blood loss after minimally invasive total knee arthroplasty: Effects of imageless navigation. Kaohsiung J Med Sci 26(5):237\u0026ndash;243\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang CW, Tseng YK, Chen YN, Yang CY (2025) Utilizing evolved extramedullary techniques for conventional knee arthroplasty in post-traumatic knee arthritis with retained hardware: A retrospective analysis. Cureus 17:e79402\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKo PS, Tio MK, Tang YK, Tsang WL, Lam JJ (2003) Sealing the intramedullary femoral canal with autologous bone plug in total knee arthroplasty. J Arthroplasty 18(1):6\u0026ndash;9\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNadler SB, Hidalgo JU, Bloch T (1962) Prediction of blood volume in normal human adults. Surgery 51:224\u0026ndash;232\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGross JB (1983) Estimating allowable blood loss: Corrected for dilution. Anesthesiology 58:277\u0026ndash;280\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTillett ED, Engh GA, Petersen T (1988) A comparative study of extramedullary and intramedullary alignment systems in total knee arthroplasty. Clin Orthop Relat Res ;(230):176\u0026ndash;181\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEngh GA, Petersen TL (1990) Comparative experience with intramedullary and extramedullary alignment in total knee arthroplasty. J Arthroplasty 5(1):1\u0026ndash;8\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuring C, Bathis H, Tingart M, Perlick L, Grifka J (2006) Computer assistance in total knee replacement: A critical assessment of current health care technology. Comput Aided Surg 11(2):77\u0026ndash;80\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrasad N, Padmanabhan V, Mullaji A (2007) Blood loss in total knee arthroplasty: An analysis of risk factors. Int Orthop 31(1):39\u0026ndash;44\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith TO, Hing CB (2010) Is a tourniquet beneficial in total knee replacement surgery? A meta-analysis and systematic review. Knee 17(2):141\u0026ndash;147\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM (2011) Tranexamic acid in total knee replacement: A systematic review and meta-analysis. J Bone Joint Surg Br 93(12):1577\u0026ndash;1585\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTai TW, Jou IM, Chang CW, Lai KA, Lin CJ, Yang CY (2010) Non-drainage is better than 4-hour clamping drainage in total knee arthroplasty. Orthopedics ;33(3)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang CW, Lan SM, Tai TW, Lai KA, Yang CY (2012) An effective method to reduce ischemia time during total knee arthroplasty. J Formos Med Assoc 111(1):19\u0026ndash;23\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThienpont E, Paternostre F, Pietsch M, Hafez M, Howell S (2013) Total knee arthroplasty with patient-specific instruments improves function and restores limb alignment in patients with extra-articular deformity. Knee 20(6):407\u0026ndash;411\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYaffe M, Luo M, Goyal N et al (2014) Clinical, functional, and radiographic outcomes following total knee arthroplasty with patient-specific instrumentation, computer-assisted surgery, and manual instrumentation: A short-term follow-up study. Int J Comput Assist Radiol Surg 9(5):837\u0026ndash;844\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalairajah Y, Cossey AJ, Verrall GM, Ludbrook G, Spriggins AJ (2006) Are systemic emboli reduced in computer-assisted knee surgery? A prospective, randomised, clinical trial. J Bone Joint Surg Br 88(2):198\u0026ndash;202\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSehat KR, Evans R, Newman JH (2000) How much blood is really lost in total knee arthroplasty? Correct blood loss management should take hidden loss into account. Knee 7(3):151\u0026ndash;155\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeyse TJ, Haas SB, Drinkwater D et al (2014) Intraarticular fibrinogen does not reduce blood loss in TKA: A randomized clinical trial. Clin Orthop Relat Res 472(1):272\u0026ndash;276\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Total knee arthroplasty, extramedullary femoral referencing, medullary canal preservation, perioperative outcomes, alignment accuracy, surgical technique","lastPublishedDoi":"10.21203/rs.3.rs-8575044/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8575044/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose-\u003c/h2\u003e \u003cp\u003eIntramedullary (IM) femoral referencing during total knee arthroplasty (TKA) has been associated with increased perioperative blood loss. This study aimed to evaluate whether a simplified extramedullary (EM) free-hand referencing technique, designed to preserve the femoral medullary canal, is associated with differences in perioperative bleeding-related parameters and alignment accuracy compared with conventional IM referencing.\u003c/p\u003e\u003ch2\u003eMethods-\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted including patients who underwent primary TKA using either IM or EM femoral referencing by a single surgeon. Perioperative hemoglobin change, calculated estimated blood loss, and postoperative D-dimer levels were analyzed as comparative bleeding-related parameters. Operative time, transfusion rates, early recovery indicators, and radiographic alignment outcomes were also assessed. All patients were managed under a standardized perioperative blood management protocol, including routine tranexamic acid administration.\u003c/p\u003e\u003ch2\u003eResults-\u003c/h2\u003e \u003cp\u003eA total of 125 TKAs were analyzed (IM: 60; EM: 65). Operative time was comparable between groups. The EM group demonstrated a smaller postoperative hemoglobin decrease (1.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 vs. 2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 g/dL; p\u0026thinsp;=\u0026thinsp;0.022) and lower calculated estimated blood loss (618.4\u0026thinsp;\u0026plusmn;\u0026thinsp;291.5 vs. 755.8\u0026thinsp;\u0026plusmn;\u0026thinsp;272.1 mL; p\u0026thinsp;=\u0026thinsp;0.008). Postoperative D-dimer levels at 24 hours were lower in the EM group (p\u0026thinsp;=\u0026thinsp;0.015) and were analyzed as an exploratory marker of perioperative physiological response. Transfusion rates were low and comparable between groups. Radiographic alignment accuracy did not differ significantly between techniques.\u003c/p\u003e\u003ch2\u003eConclusion-\u003c/h2\u003e \u003cp\u003eFemoral medullary canal preservation using a simplified extramedullary free-hand referencing technique was associated with favorable perioperative bleeding-related parameters without compromising alignment accuracy or operative efficiency. This approach represents a practical alternative to intramedullary referencing in primary TKA and warrants further prospective evaluation.\u003c/p\u003e\u003ch2\u003eLevel of Evidence\u003c/h2\u003e \u003cp\u003eIII\u003c/p\u003e","manuscriptTitle":"Impact of Femoral Medullary Canal Preservation During Primary Total Knee Arthroplasty on Early Perioperative Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 12:18:38","doi":"10.21203/rs.3.rs-8575044/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"26c0069a-3805-442e-9454-011729bdbdf1","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-29T18:24:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 12:18:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8575044","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8575044","identity":"rs-8575044","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}